The pathogenesis of radiation leukemia virus (RadLV) induced murine leukemia as well as spontaneous leukemia in high leukemia strains of mice develops through dependent phases towards the autonomous growth of leukemic lymphoblasts. This can be demonstrated by the presence of preleukemic lymphocytes (PLC) in the bone marrow. PLC, when transferred into irradiated F1 hybrid hosts, give rise to donor type leukemia. It seems, therefore, that the appearance of leukemic cells is preceeded by essentially transformed precursors, the final transformation of which depends on coleukemogenic effects, like irradiation. We propose to analyse genetically defined mechanisms involved in the different steps of pathogenesis: 1) We will study the role of H-2 linked Ir genes in the immunological arrest of PLC. 2) The role of Fv-1 like genes in the switch from preleukemic to autonomous growth, possibly involving recombinant viruses, will be also investigated. 3) Experiments to clarify the target cell specificity of RadLV in H-2 linked resistant versus sensitive haplotypes will be undertaken. These latter experiments are based on the hypothesis that the H-2 complex may be involved in the regulation of cellular receptors for RadLV. In the proposed study cellular immunological, tumor transplantation, cell fractionation and virological methods will be employed.